Novel strategies for managing pancreatic cancer

Table 1 Desired characteristics for a nanoparticle drug-delivery platform

Desired characteristic	Comments
Inherently non-toxic materials and degradation products	The initial material selection should be based on non-toxic materials especially with an aim toward human health care
Small size (10–200 nm)	There is not a particular size that seems most efficacious, particularly based on in vivo studies. This is the range of particle diameters that have proven most effective for a wide variety of delivery systems. Also of note is the debate around the influence of particle shape[83]
Encapsulation of active agent	To be effective, the active agent must be encapsulated within the nanoparticle vehicle. Surface decoration (i.e., adsorption) will often be effective in vitro but falls short for in vivo studies because of the reticulum endoplasmic systems in vivo
Colloidally stable in physiological conditions	The nanoparticle vehicle and surface functionalization must resist agglomeration for the solution pH values, ionic strength, macromolecular interactions, and temperature encountered in the physiological environment
Clearance mechanism	The nanoparticle vehicle must have a ready clearance mechanism to avoid the cumulative and/or systemic effects of the drug-laden particles
Long clearance times	Resistance to agglomeration and other effects that remove the nanoparticle-encapsulated drug from the patient must be avoided to promote long circulation times in the circulatory system for as many of the nanoparticles to find and sequester in the cancer cells as possible
Biologically or extrinsically controlled release of therapeutic agents	There should be a trigger mechanism such as the acidic pH within the tumor or during endosome maturation designed into the nanoparticle platform to ensure the release of the encapsulated drug into the targeted tissue
Can be targeted to cell/tissue of choice	The nanoparticle platform should be capable of surface bioconjugation to target molecules for the specific cancer to provide the greatest uptake with the lesions and fewest least side effects with healthy tissue

Reprinted with permission from [71]. Copyright 2010 American Chemical Society.

Table 2 The selection criteria for nanomaterial drug delivery systems

Nano particulate material	Size (nm)	Therapeutic agent(s) carried	Advantages	Limitations
Biodegradable polymers	10-100	Plasmid DNA, proteins, peptides, low molecular-weight (MW) organic compounds	Sustained localized drug delivery for weeks	Exocytosis of undissolved nanoparticles. Fixed functionality after synthesis may require new synthetic pathways for alternate surface functionalities
Ceramic	< 100	Proteins, DNA, chemotherapeutic agents, high MW organic compounds	Easily prepared, water dispersible, stable in biological environments	Toxicity of materials, exocytosis of undissolved nanoparticles, time consuming synthesis, surface decoration instead of encapsulation
Metals	< 50	Proteins, DNA, chemotherapeutic agents	Small particles present a large surface area for surface decoration delivery	Toxicity of materials, exocytosis of undissolved nanoparticles, time consuming synthesis, surface decoration instead of encapsulation
Polymeric micelles	< 100	Proteins, DNA, chemotherapeutic agents	Suitable for water-insoluble drugs due to hydrophobic core	Toxicity of materials, fixed functionality after synthesis
Dendrimers	< 10	Chemotherapeutic agents, anti-bacterial, anti-viral agents, DNA, high MW organic compounds	Suitable for hydrophobic or hydrophilic drugs	May use toxic materials, time consuming synthesis, fixed functionality after synthesis may require new synthetic pathways for alternate surface functionalities
Liposomes	50-100	Chemotherapeutic agents, proteins, DNA	Reduced systemic toxicity, increased circulation time	Fixed functionality after synthesis, some leakage of encapsulated agent, lack of colloidal stability
3D printing	20-2000	Chemotherapeutic agents, proteins, DNA, imaging agents	Precise control over size, shape, and surface functionalization. 3D printing can be used with an array of processing techniques to create porous scaffolds[85] and lab-on-chip devices[86] for personalized medicine[87]	Toxicity of materials depending on material
Calcium phosphosilicate	20-60	Chemotherapeutic agents, RNA, high and low MW organic compounds, imaging agents	Simple preparation, suitable for hydrophilic or hydrophobic drugs, colloidal stability in physiological environments, pH-dependent dissolution results in intracellular delivery of drugs, composed of bio-resorbable material	Encapsulated materials limited to solubility in water or organic solvent

Reprinted and updated with permission from [71] which contains material adapted from [84]. Copyright 2010 American Chemical Society.